Exercise + Liraglutide for Metabolic Syndrome

(ZQL008 Trial)

Overseen By Linda Jahn, MEd

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Virginia

Must not be taking: Diabetes medications, Liraglutide

Disqualifiers: Diabetes, Smoking, Hypertriglyceridemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to examine whether exercise training alone, liraglutide treatment alone or exercise training plus liraglutide treatment increases cardiac and skeletal muscle microvascular blood volume, improves vascular function of the conduit vessels, and enhances insulin's metabolic action in humans with Metabolic Syndrome. Subjects will be randomized to one of the 4 groups: control, exercise training, liraglutide treatment, and exercise + liraglutide. They will be studied at the baseline and then after 24 weeks of intervention.

Do I need to stop my current medications for the trial?

You can continue taking certain medications if the doses have been stable for at least 3 months. These include medications like ACE inhibitors, ARBs, statins, and others listed in the trial criteria.

What data supports the effectiveness of the treatment Exercise + Liraglutide for Metabolic Syndrome?

Research shows that regular exercise can improve blood sugar control, insulin sensitivity, and reduce risk factors for heart disease in people with metabolic syndrome. Exercise is as effective as some diabetes medications in managing blood sugar levels and can also help with weight loss when combined with a healthy diet. ^{1 2 3 4 5}

Is the combination of exercise and liraglutide safe for humans?

Liraglutide, used for managing obesity and type 2 diabetes, is generally safe for humans, with mild to moderate stomach-related side effects that usually decrease over time. It has a low risk of causing low blood sugar and is well-tolerated when combined with diet and exercise. ^{6 7 8 9 10}

How does the treatment of exercise and liraglutide differ from other treatments for metabolic syndrome?

This treatment combines exercise, which improves insulin sensitivity and body composition, with liraglutide, a medication that helps control blood sugar levels and supports weight loss. This dual approach targets multiple aspects of metabolic syndrome, potentially offering more comprehensive benefits than treatments focusing on a single component. ^{1 2 11 12 13}

Research Team

Zhenqi Liu, MD

Principal Investigator

Division of Endocrinology and Metabolism, University of Virginia

Eligibility Criteria

Adults aged 21-60 with Metabolic Syndrome, not currently very active, and have a stable weight (BMI between 25-35) can join. They must meet at least three criteria like large waist size, high triglycerides or blood sugar, low HDL cholesterol, or high blood pressure. Those on certain stable medications may also qualify.

Inclusion Criteria

I meet at least 3 of the 5 criteria for Metabolic Syndrome.

I am between 21 and 60 years old.

Your "good" cholesterol (HDL) is too low.

Exclusion Criteria

I have diabetes or have taken medication for it.

You have been regularly doing intense exercise for at least 20 minutes, two times a week.

You have very high levels of triglycerides or cholesterol in your blood.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of four groups: control, exercise training, liraglutide treatment, or exercise + liraglutide for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Exercise training
• Liraglutide

Trial Overview The study is testing the effects of exercise alone, the drug Liraglutide alone, and both combined on heart and muscle blood flow and insulin function in people with Metabolic Syndrome over 24 weeks. Participants will be randomly placed into one of four groups including a control group.

Participant Groups

Group I: Liraglutide Alone Experimental Treatment 1 Intervention

24 weeks of treatment

Group II: Exercise Alone Experimental Treatment 1 Intervention

24 weeks of treatment

Group III: Exercise + Liraglutide Experimental Treatment 1 Intervention

24 weeks f treatment

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Increased daily physical activity can prevent type 2 diabetes and help treat metabolic syndrome, showing effects on glycaemic control comparable to oral antidiabetic medications.

Exercise, whether endurance or strength training, improves insulin resistance and body composition, and when combined with a proper diet, can also help correct issues like dyslipidaemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical training in the treatment of metabolic syndrome]. Dela, F.[2017]

Supervised, long-term moderate to moderately vigorous exercise training can significantly improve lipid profiles in overweight and obese adults with metabolic syndrome, even without weight loss, by increasing HDL cholesterol and decreasing triglycerides.

Lifestyle changes, including exercise and dietary modifications, are crucial for improving insulin resistance and glucose tolerance, and they play a key role in preventing or delaying type 2 diabetes in individuals at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. Carroll, S., Dudfield, M.[2022]

Regular exercise can significantly improve glycemic control and reduce risk factors for coronary heart disease in individuals with type II diabetes, particularly by enhancing insulin sensitivity.

There is a notable lack of research on the effects of exercise specifically in Black individuals with type II diabetes, despite their higher prevalence of the condition and associated cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in therapy and prevention of type II diabetes. Implications for blacks. Ruderman, N., Apelian, AZ., Schneider, SH.[2022]

Structured endurance exercise can significantly improve glycemic control, insulin sensitivity, and cardiovascular risk factors in individuals with Type 2 diabetes, showing effects comparable to standard medications.

While exercise is beneficial, adherence to structured programs can be challenging, and more research is needed to understand the impact of lifestyle-based physical activity and the specific types and amounts of exercise that are most effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting the role of physical activity and exercise in the treatment of type 2 diabetes. Tudor-Locke, CE., Bell, RC., Meyers, AM.[2019]

Regular physical activity leads to significant metabolic and cardiovascular adaptations that can improve insulin resistance, which is crucial for managing metabolic syndrome.

Patient motivation and adherence to exercise therapy are essential for achieving positive treatment outcomes in individuals with metabolic syndrome, highlighting the need for a comprehensive approach to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exercise therapy for patients with metabolic syndrome]. Svacinová, H.[2017]

Liraglutide, now available at a higher dose of 3.0 mg for treating obesity, has been shown to effectively control appetite and promote weight loss when combined with diet and exercise, based on results from the SCALE studies.

The drug is already established for managing type 2 diabetes at lower doses, and its mechanism of action includes effects on the endocrine pancreas and appetite regulation in the hypothalamus, indicating a dual benefit for patients with obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY]. Scheen, AJ.[2016]

Liraglutide, approved for Type 2 diabetes and chronic weight management, works by increasing insulin secretion and decreasing appetite, which helps promote weight loss.

Recent findings suggest that liraglutide may also protect against prediabetes and prevent bone loss by enhancing bone formation after weight loss, highlighting its broader health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide for Type 2 diabetes and obesity: a 2015 update. Iepsen, EW., Torekov, SS., Holst, JJ.[2015]

Liraglutide (Saxenda) has been shown to effectively promote weight loss in overweight and obese patients, with a higher percentage achieving 5% and 10% weight loss compared to placebo and orlistat, based on randomized controlled studies.

The medication is generally safe, with gastrointestinal side effects being the most common and typically dose-dependent, making it a viable adjunct to lifestyle changes for obesity management, especially in patients with prediabetes and women with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide: an injectable option for the management of obesity. Clements, JN., Shealy, KM.[2022]

Liraglutide is an effective treatment for type 2 diabetes, showing greater improvement in glycemic control compared to other incretin-based therapies, with sustained benefits observed over a period of up to 2 years.

The medication is generally well tolerated, with a low risk of hypoglycemia and mild to moderate gastrointestinal side effects that decrease with continued use, while also offering additional benefits like weight reduction and improved beta-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide in type 2 diabetes mellitus. Baruah, MP., Chaudhury, T., Sethi, BK., et al.[2018]

Liraglutide is an effective treatment for type 2 diabetes, reducing hemoglobin A1c levels by 0.8% to 1.5%, and is safe for patients at risk of hypoglycemia due to its low incidence of this side effect.

It is particularly beneficial for overweight or obese patients, as it not only helps control blood sugar but also promotes weight loss of about 2%-4% of initial body weight, although nausea can occur but is typically manageable with careful dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. Gross, B.[2015]

Exercise training significantly improves insulin sensitivity, glucose tolerance, and lowers triglyceride and cholesterol levels in nondiabetic, nonobese individuals with hypertriglyceridemia, but these benefits are not observed in patients with impaired glucose tolerance.

In severely obese individuals without diabetes, combining exercise with a calorie-restricted diet enhances insulin sensitivity, while in obese patients with non-insulin dependent diabetes, adding exercise to sulfonylurea therapy improves insulin sensitivity and reduces glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus. Lampman, RM., Schteingart, DE.[2007]

In diabetics, the metabolic response to exercise is influenced by insulin availability, with acute exercise lowering blood glucose in insulin-dependent patients but potentially increasing it in insulin-deficient, ketotic patients.

Regular exercise improves insulin sensitivity and positively affects lipid metabolism, which may benefit diabetic patients by enhancing their overall metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in diabetes: therapeutic implications. Koivisto, VA., Sherwin, RS.[2019]

Insulin resistance and hyperinsulinemia are key features of metabolic syndrome, which can lead to serious health issues like type 2 diabetes and cardiovascular disease, but regular exercise and calorie restriction can improve insulin sensitivity.

The review highlights that AMP-activated protein kinase (AMPK) plays a crucial role in regulating insulin sensitivity and may be a promising target for preventing and treating metabolic syndrome-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPK, insulin resistance, and the metabolic syndrome. Ruderman, NB., Carling, D., Prentki, M., et al.[2022]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

[Physical training in the treatment of metabolic syndrome]. [2017]

2. New Zealand pubmed.ncbi.nlm.nih.gov

What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Exercise in therapy and prevention of type II diabetes. Implications for blacks. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Revisiting the role of physical activity and exercise in the treatment of type 2 diabetes. [2019]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

[Exercise therapy for patients with metabolic syndrome]. [2017]

6. Belgium pubmed.ncbi.nlm.nih.gov

[LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY]. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Liraglutide for Type 2 diabetes and obesity: a 2015 update. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Liraglutide: an injectable option for the management of obesity. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Liraglutide in type 2 diabetes mellitus. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus. [2007]

12. England pubmed.ncbi.nlm.nih.gov

Exercise in diabetes: therapeutic implications. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

AMPK, insulin resistance, and the metabolic syndrome. [2022]